: Despite its mandate on minimizing harms in clinical trials, the Common Rule provides little guidance as to how IRBs should evaluate risk. The Common Rule and derivative commentaries tend to conceptualize risk review as an expert-based endeavor aimed at an objective and universal evaluation of possible harm; they also have tended to locate risk in the research activity itself rather than in the context of the research. These views of risk conflict with scholarship showing that risk evaluations are socially (...) determined even among experts, that the context of harms can influence how persons evaluate risks, and that forums that approach risk assessment as a technical endeavor bracket from discussion the numerous values that ground risk judgments. Possible reforms are proposed for clinical trial risk review that would render it more inclusive of the different types of risks encountered and more attuned to the priorities of trial subjects. (shrink)

Minimal risk is a central concept in the ethical analysis of research with children. It is defined as the risks “. . . ordinarily encountered in daily life . . . .” But the question arises: who is the referent for minimal risk? Commentators in the research ethics literature often answer this question by endorsing one of two possible interpretations: the uniform interpretation or the relative interpretation of minimal risk. We argue that describing the debate over minimal risk as a (...) disagreement between the uniform and the relative interpretation impedes progress on the identification of a justifiable referent for minimal risk. There are two main problems with this approach: constructing the debate over minimal risk as a disagreement between a uniform and a relative interpretation misconstrues the main difference between competing interpretations and neither the uniform nor the relative interpretation identifies one unique and consistent group of children as the referent for minimal risk. We conclude that progress on the debate over minimal risk requires that we abandon the uniform and relative interpretations and address the main moral problem at stake: whether healthy children or the subjects of the research should be the referent for minimal risk. (shrink)

The American Journal of Bioethics, Volume 11, Issue 6, Page 27-29, June 2011.

In Grimes v. Kennedy Krieger Institute, the Maryland Court of Appeals considered whether it is possible for investigators or research entities to have a special relationship with subjects, thereby creating a duty of care that could, if breached, give rise to an action in negligence. The research under review, the Lead Abatement and Repair & Maintenance Study, was conducted from 1993 to 1996 by investigators at the Kennedy Krieger Institute, an affiliate of Johns Hopkins University.After briefly discussing the case at (...) the center of this ruling, I consider how ambiguities within the federal research regulations at 45 C.F.R. § 46 contribute to disagreements among reasonable and informed people of good will about what studies should be approved. I argue that Grimes may be understood as placing restrictions on how these regulations may be interpreted and used. (shrink)

The concept of minimal risk plays a key role in federal regulations on the protection of human research subjects. Although there has been considerable discussion of the meaning of minimal risk, the question of how this concept should be interpreted in research involving pregnant women and fetuses has not been addressed. This essay reviews the literature on minimal risk and argues for an interpretation of that concept in the context of research involving pregnant women and fetuses.

How should the definition of “minimal risk” in the federal research regulations be interpreted in regard to pregnant women and fetuses? Surprisingly, there has been little discussion of this question. There is, after all, a substantial amount of published work addressing the question of how “minimal risk” should be interpreted. Similarly, there is a large body of literature on the ethics of research involving pregnant women and fetuses, particularly maternal-fetal surgery. However, in neither of these bodies of work can one (...) find an analysis of minimal risk in regard to fetuses or pregnant women.The concept of minimal risk is defined in the regulations as follows:Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. (shrink)

When may a physician enroll a patient in clinical research? An adequate answer to this question requires clarification of trust-based obligations of the state and the physician-researcher respectively to the patient-subject. The state relies on the voluntarism of patient-subjects to advance the public interest in science. Accordingly, it is obligated to protect the agent-neutral interests of patient-subjects through promulgating standards that secure these interests. Component analysis is the only comprehensive and systematic specification of regulatory standards for benefit-harm evaluation by research (...) ethics committees (RECs). Clinical equipoise, a standard in component analysis, ensures the treatment arms of a randomised control trial are consistent with competent medical care. It thus serves to protect agent-neutral welfare interests of the patient-subject. But REC review occurs prior to enrolment, highlighting the independent responsibility of the physician-researcher to protect the agent-relative welfare interests of the patient-subject. In a novel interpretation of the duty of care, we argue for a “clinical judgment principle” which requires the physician-researcher to exercise judgment in the interests of the patient-subject taking into account evidence on treatments and the patient-subject‘s circumstances. (shrink)

In Grimes v. Kennedy Krieger Institute, the Maryland Court of Appeals considered whether it is possible for investigators or research entities to have a special relationship with subjects, thereby creating a duty of care that could, if breached, give rise to an action in negligence. The research under review, the Lead Abatement and Repair & Maintenance Study, was conducted from 1993 to 1996 by investigators at the Kennedy Krieger Institute, an affiliate of Johns Hopkins University.After briefly discussing the case at (...) the center of this ruling, I consider how ambiguities within the federal research regulations at 45 C.F.R. § 46 contribute to disagreements among reasonable and informed people of good will about what studies should be approved. I argue that Grimes may be understood as placing restrictions on how these regulations may be interpreted and used. (shrink)

This thesis is a contribution to the ethical justification for clinical research with children. A research subject’s participation in a trial is usually justified, in part, by informed consent. Informed consent helps to uphold the moral principle of respect for persons. But children’s limited ability to make informed choices gives rise to a problem. It is unclear what, if anything, justifies their participation in research. Some research ethicists propose to resolve this problem by appealing to social utility, proxy consent, arguments (...) explaining why it is permissible to expose children to some harm, and an argument concerning the appropriate balance between research harms and benefits. I argue that each of these is a necessary part of the justification for research with children, but that the argument concerning harms and benefits is under-developed. It relies on the concept of minimal risk, but minimal risk is inadequately justified. I propose an interpretation of minimal risk. I defend the idea that minimal risk should be interpreted according to the risks of daily life. I reject the most prominent defense of daily life, which claims that daily risks are morally relevant because they replace, rather than add to, the risks a child would ordinarily face. Instead, I propose that these risks are part of a reasonable trade-off between personal safety and our ability to pursue meaningful lives. I then examine whose daily life should be captured in the concept of minimal risk. I reject arguments that minimal risk should refer to healthy children or the subjects of the research and propose instead that the referent should be children who are not unduly burdened by their lives. I argue that children are not unduly burdened when they fare well and defend the idea that children fare well when they possess sufficiently high degrees of the substantive goods of childhood. I conclude by analyzing a controversial case study using my interpretation of minimal risk. I draw on this case to argue that my interpretation offers clear guidance for research ethics review and contributes to a determination that is more plausible than its rivals. (shrink)

The American Journal of Bioethics, Volume 11, Issue 6, Page 25-27, June 2011.